Stroke is a major complication of children with sickle cell anemia (SCA), and several major studies have demonstrated that 25% of children with SCA have evidence of infarction at the time of cerebral MRI studies. Approximately 8-10% of children with SCA suffer from symptomatic stroke, while up to 18% or more have silent stroke. The peak age for symptomatic stroke is 2-5 years, and complications of stroke in patients with SCA include school failure, motor handicaps and seizure disorders. The majority of strokes in children are the result of progressive occlusion of the major intracranial vessels, but the pathophysiology of stroke is largely unknown. Histopathologic interpretation of vessel involvement demonstrates endothelial damage and fibrosis. It is of interest therefore, that there is increasing recognition of the involvement of the immune system in diseases characterized by endothelial injury such as Moya Moya disease. Since the Moya Moya-like changes seen in patients with SCA are pathologically similar to those in Moya Moya disease, in a preliminary study the investigators investigated whether HLA type was associated with stroke in 54 children with SCA. These data demonstrated a significant association between HLA phenotype and stroke. The investigator was first to find a multigenic influence on stroke risk in SCA. Other preliminary data were presented which demonstrated a preliminary screen for markers potentially associated with stroke in 69 children with SCA. These data demonstrated that particular alleles may be associated with stroke risk, but the small sample size precluded statistical significance and the effects of multiple genes could not be assessed in the small sample size. Of note, stroke in SCD is likely to be the result of both genetic and environmental factors, and anecdotal evidence suggests that stroke occurs often in siblings with SCA. Finally, transcranial Doppler ultrasound is the only diagnostic modality which has been shown to be useful in identifying patients at risk for symptomatic stroke; unfortunately there is as yet no test for children at risk for silent infarct. The objectives of this study are to evaluate the possibility of a multigenic involvement in stroke in SCA by simultaneously assessing multiple genetic loci. The specific aims include the following: 1.) Identification of candidate genes influencing stroke risk in children with SCA using a novel, PCR-based multiplex assay; 2.) Correlation of the interactions between specific clinical and genetic factors on the risk of stroke in children with SCA; and 3.) Development of a new PCR-based multiplex assay strip specifically for use in assessing stroke risk in children with SCA.